Ancient disease resistance made us vulnerable to HIV

Early immune resistance may have helped to set stage for modern pandemic.

Humans may be susceptible to infection by HIV because our ancient ancestors evolved resistance to another virus.

That's the conclusion reached by geneticists who have compared our own genome sequence with that of apes, in search of signs
of old viral attacks. The researchers wondered whether chimps had been battered by a virus that humans had evolved a resistance
to, and whether that resistance might shed some light on our modern susceptibility to other viruses. Their hunch was right.

The group found that the DNA of our closest evolutionary relatives is riddled with the hallmarks of a now-extinct virus called
PtERV1. This virus probably infected chimpanzees and other apes around four million years ago — after chimps' evolutionary
split from humans. Chimps were badly hit by the virus. But humans, it seems, could fight it off. Unfortunately, the defensive
protein that protects against PtERV1 seems to increase our cells' susceptibility to HIV attack, report Michael Emerman and
his colleagues at the Fred Hutchinson Cancer Research Center in Seattle.

PtERV1, like HIV, is a 'retrovirus' — it contains RNA that is converted into DNA within the host cell and then inserted into
the host genome. Throughout evolution, such viruses leave a legacy as their DNA is passed on from generation to generation,
ultimately becoming present in the entire host population. Roughly 8% of human DNA is made up of these viral leftovers.

Emerman and his team scoured the chimpanzee genome and found around 130 copies of DNA sequences from PtERV1. But as they report
in this week's Science1, not one copy of this viral DNA has been incorporated into the human genome, meaning that something must have fought it off.

Single defence

Emerman and his colleagues used the chimpanzee DNA to reconstruct part of the virus in the lab. They then tried to infect
human cells in culture with it, and found that a protein called TRIM5??prevented the virus from entering human cells. When
this protein was removed from human cells, the cells were vulnerable to the reconstructed virus; but they were also less susceptible
to infection by HIV.

No one is sure why this should be the case, but the researchers suspect that the ancient human immune system might have 'put
all its eggs in one basket' as far as defending against retroviruses was concerned. Humans don't seem to have any immune defensive
measures against retroviruses other than TRIM5.

This immune strategy must have carried an evolutionary advantage millions of years ago, Emerman says, "The most obvious benefit
is that this protected some humans from disease." But he adds that "we don't really know anything about what sort of disease
PtERV1 might have caused."

Unfortunately, the discovery does not hold much promise for efforts to find a vaccine against HIV/AIDS, says Emerma. "I do
not see much insight of this work into vaccines, although maybe others can," he says. "I see this work more along the lines
of understanding human history by uncovering the past — sort of like archaeology or palaeontology."

What the work does do is spotlight how the human immune system came to be the way it is today. "Our host defence genes have
been shaped by a long history of genetic conflict with ancient viruses. If we want to understand why our defences are the
way they are, the answers inevitably lie in these ancient viruses, more so than in the ones that have affected us only recently,"
says Emerman.